Gain-of-function oncogenic mutations in TP53 enhance defined factor-mediated cellular reprogramming

Cancer is a disorder with various genetic and epigenetic alterations. Genetic alterations such as mutations, i.e., substitutions, amplifications, and deletions of nucleotide sequences, are largely irreversible, whereas epigenetic alterations can be modified by pharmacological agents that target components of the epigenetic machinery. Recent studies have showed that introduction of defined factors such as those encoded by c-MYC, SOX2, OCT3/4, and KLF4 in normal somatic cells results in their dedifferentiation into induced pluripotent stem (iPS) cells. In addition, we have reported that these iPS factors induce the development of induced multipotent cancer (iPC) cells from gastrointestinal cancer cells by reducing tumor aggressiveness. The efficiency of iPS reprogramming increased when p53 was inhibited. The study of cancer cells suggests that the p53 pathways might be involved in the aggressive phenotypes of iPC cells in a long-term culture. However, the roles of gain-of-function oncogenic mutations in TP53, which is a key tumor suppressor gene, remain to be elucidated. We investigated reprogramming efficiency of iPS generation in human diploid fibroblasts that were co-transfected with TP53 mutants and defined factors. The results suggest that mutations in those TP53 regions that are involved in DNA contact might play a critical role in the efficiency of iPS generation. Taken together, our studies suggest 2 roles of TP53 mutations in reprogramming: (1) the structural mutations might contribute to, or collaborate with, other mutations to regulate the maintenance of genomic stability; (2) the DNA-contact mutations could affect the downstream target genes, which may be distinct from those involved in wild-type p53 function. These molecular manipulations of tumorigenicity and enhancement of cellular reprogramming efficiency by the p53 pathway will open an attractive and useful avenue for future medicine

Development and evaluation of a master-slave robot system for single-incision laparoscopic surgery

Single-incision laparoscopic surgery (SILS) brings cosmetic benefits for patients, but this procedure is more difficult than laparoscopic surgery. In order to reduce surgeons' burden, we have developed a master-slave robot system which can provide robot-assisted SILS as if it were performing conventional laparoscopic surgery and confirmed the feasibility of our proposed system. The proposed system is composed of an input device (master side), a surgical robot system (slave side), and a control PC. To perform SILS in the same style as regular laparoscopic surgery, input instruments are inserted into multiple incisions, and the tip position and pose of the left-sided (right-sided) robotic instrument on the slave side follow those of the right-sided (left-sided) input instruments on the master side by means of a control command from the PC. To validate the proposed system, we defined four operating conditions and conducted simulation experiments and physical experiments with surgeons under these conditions, then compared the results. In the simulation experiments, we found learning effects between trials (P = 0.00013 0.1), and the task time of our system was significantly shorter than the simulated SILS (P = 0.011 < 0.05). In the physical experiments, our system performed SILS more easily, efficiently, and intuitively than the other operating conditions. Our proposed system enabled the surgeons to perform SILS as if they were operating conventionally with laparoscopic techniques.ArticleINTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY. 7(2):289-296 (2012)journal articl

Laparoscopic Bladder-Preserving Surgery for Enterovesical Fistula Complicated with Benign Gastrointestinal Disease

Enterovesical fistula (EVF) is a relatively uncommon condition that is associated with severe morbidity. Minimally invasive and organ-preserving surgery should be performed in the case of EVF caused by benign diseases. We applied laparoscopic bladder-preserving surgery (LBPS) for EVF caused by benign gastrointestinal disease. Here, we report a surgical technique for LBPS. Patient and instrument port positioning are similar to those used in laparoscopic colorectal surgery. Dissection around the fistula is performed along the intestine as distant from the bladder as possible. If there is sufficient area around the intestinal portion of the fistula, it is isolated and resected using a linear stapler. If this approach is not possible, the intestinal fistula is sharply dissected as far away from the bladder as possible. LBPS for EVF was performed in 4 patients and included 3 direct sharp dissections and 1 stapling dissection. Three of the 4 patients did not require any further treatment for the bladder, and all procedures were feasibly accomplished under laparoscopic conditions. In conclusion, LBPS is feasible in cases of EVF caused by benign gastrointestinal disease, and we suggest that it should be the first choice of intervention in such cases

A four-dimensional organoid system to visualize cancer cell vascular invasion

Yanagisawa, K.; Konno, M.; Liu, H.; Irie, S.; Mizushima, T.; Mori, M.; Doki, Y.; Eguchi, H.; Matsusaki, M.; Ishii, H. A Four-Dimensional Organoid System to Visualize Cancer Cell Vascular Invasion. Biology 2020, 9, 361

Efficacy of human resource development program for young industry personnel who will be involved in future medical device development

Background: Training next-generation personnel from small/medium enterprises (SMEs) is an urgent issue in promoting medical device research and development (R&D). Since 2014 we have engaged in governmentally funded human resource development program for medical/non-medical SMEs, and have assessed its effectiveness by analyzing self-evaluation of achievement level (SEAL) data obtained before and after the training course. Methods: Human resource development experts interviewed 34 key opinion leaders with deep knowledge of medical device R&D from industry, government, and academia. The skills required for R&D personnel were written down, and a set of skills was created by making a greatest common measure in the list of common elements among them. Using that skill sets, skill evaluations were conducted on trainees at “Osaka University Training Course,” twice before participation and after completion of the entire program using SEAL assessment. Results: There were 97 men and 25 women, with one-third in the’30 s. Among them, 61 participants (50%) were from R&D divisions, and 32 (26%) were from business/sales divisions. 94 (77%) were from medical SMEs, and 28 (23%) were from non-medical SMEs (new entry). After completing the training course, significant growth was observed in every item of both Soft and Hard skill sets. Especially in new entry SME members, a striking improvement was observed in practical medical knowledge to enhance communication with medical doctors (p < 0.0001). Conclusion: Our training course, though 7-day-short in total, showed that both Soft and Hard skills could be improved in young medical/non-medical SME members. Further assessment is needed to establish the necessary skill sets for our future partners from industries, to foster the creation of innovative medical devices through med-tech collaboration.The version of record of this article, first published in Surgical Endoscopy, is available online at Publisher’s website: https://doi.org/10.1007/s00464-023-10474-

Convolutional neural network can recognize drug resistance of single cancer cells

It is known that single or isolated tumor cells enter cancer patients' circulatory systems. These circulating tumor cells (CTCs) are thought to be an effective tool for diagnosing cancer malignancy. However, handling CTC samples and evaluating CTC sequence analysis results are challenging. Recently, the convolutional neural network (CNN) model, a type of deep learning model, has been increasingly adopted for medical image analyses. However, it is controversial whether cell characteristics can be identified at the single-cell level by using machine learning methods. This study intends to verify whether an AI system could classify the sensitivity of anticancer drugs, based on cell morphology during culture. We constructed a CNN based on the VGG16 model that could predict the efficiency of antitumor drugs at the single-cell level. The machine learning revealed that our model could identify the effects of antitumor drugs with ~0.80 accuracies. Our results show that, in the future, realizing precision medicine to identify effective antitumor drugs for individual patients may be possible by extracting CTCs from blood and performing classification by using an AI system

Local Resection by Combined Laparoendoscopic Surgery for Duodenal Gastrointestinal Stromal Tumor

Combined laparoendoscopic surgery is a novel surgical method which consists of both endoscopic surgery from inside the gastrointestinal tract and laparoscopic surgery from the outside. We report a case of duodenal GIST, in which combined laparoendoscopic local resection was attempted. The lesion was resected endoscopically using endoscopic submucosal dissection technique under laparoscopic assistance. Laparoscope was used for originating the orientation of the tumor, intra-operative EUS, and monitoring serosal injury from the peritoneal cavity. Postoperative hemorrhage occurred; however, precise orientation of the lesion helped us to manage the patient with minimal invasive reoperation. And thus, the bowel integrity was completely preserved, by avoiding segmental duodenal resection and pancreaticoduodenectomy. This novel, less invasive surgical procedure may become an attractive option for the lesions originating in the anatomically challenging portion of the GI tract for endoscopic or laparoscopic surgery alone